Pubertal stage and the prevalence of violence and social/relational aggression

OBJECTIVE We examined associations between pubertal stage and violent adolescent behavior and social/relational aggression.

METHODS The International Youth Development Study comprises statewide representative student samples in grades 5, 7, and 9 (N = 5769) in Washington State and Victoria, Australia, drawn as a 2-stage cluster sample in each state. We used a school-administered, self-report student survey to measure previous-year violent behavior (ie, attacking or beating up another person) and social/relational aggression (excluding peers from the group, threatening to spread lies or rumors), as well as risk and protective factors and pubertal development. Cross-sectional data were analyzed.

RESULTS Compared with early puberty, the odds of violent behavior were approximately threefold higher in midpuberty (odds ratio [OR]: 2.87 [95% confidence interval (CI): 1.81–4.55]) and late puberty (OR: 3.79 [95% CI: 2.25–6.39]) after adjustment for demographic factors. For social/relational aggression, there were weaker overall associations after adjustment, but these associations included an interaction between pubertal stage and age, and stronger associations with pubertal stage at younger age were shown (P = .003; midpuberty OR: 1.78 [95% CI: 1.20–2.63]; late puberty OR: 3.00 [95% CI: 1.95–4.63]). Associations between pubertal stage and violent behavior and social/relational aggression remained after the inclusion of social contextual mediators in the analyses.

CONCLUSIONS Pubertal stage was associated with higher rates of violent behavior and social/relational aggression, with the latter association seen only at younger ages. Puberty is an important phase at which to implement prevention programs to reduce adolescent violent and antisocial behaviors.

Structural and functional properties of human multidrug resistance protein 1 (MRP1/ABCC1)

Multidrug ABC transporters such as P-glycoprotein (P-gp/MDR1/ABCB1) and multidrug resistance protein 1 (MRP1/ABCC1) play an important role in the extrusion of drugs from the cell and their overexpression can be a cause of failure of anticancer and antimicrobial chemotherapy. Recently, the mouse P-gp/Abcb1a structure has been determined and this has significantly enhanced our understanding of the structure-activity relationship (SAR) of mammalian ABC transporters. This paper highlights our current knowledge on the structural and functional properties and the SAR of human MRP1/ABCC1. Although the crystal structure of MRP1/ABCC1 has yet to be resolved, the current topological model of MRP1/ABCC1 contains two transmembrane domains (TMD1 and TMD2) each followed by a nucleotide binding domain (NBD) plus a third NH2-terminal TMD0. MRP1/ABCC1 is expressed in the liver, kidney, intestine, brain and other tissues. MRP1/ABCC1 transports a structurally diverse array of important endogenous substances (e.g. leukotrienes and estrogen conjugates) and xenobiotics and their metabolites, including various conjugates, anticancer drugs, heavy metals, organic anions and lipids. Cells that highly express MRP1/ABCC1 confer resistance to a variety of natural product anticancer drugs such as vinca alkaloids (e.g. vincristine), anthracyclines (e.g. etoposide) and epipodophyllotoxins (e.g. doxorubicin and mitoxantrone). MRP1/ABCC1 is associated with tumor resistance which is often caused by an increased efflux and decreased intracellular accumulation of natural product anticancer drugs and other anticancer agents. However, most compounds that efficiently reverse P-gp/ABCB1-mediated multidrug resistance have only low affinity for MRP1/ABCC1 and there are only a few effective and relatively specific MRP1/ABCC1 inhibitors available. A number of site-directed mutagenesis studies, biophysical and photolabeling studies, SAR and QSAR, molecular docking and homology modeling studies have documented the role of multiple residues in determining the substrate specificity and inhibitor selectivity of MRP1/ABCC1. Most of these residues are located in the TMs of TMD1 and TMD2, in particular TMs 4, 6, 7, 8, 10, 11, 14, 16, and 17, or in close proximity to the membrane/cytosol interface of MRP1/ABCC1. The exact transporting mechanism of MRP1/ABCC1 is unclear. MRP1/ABCC1 and other multidrug transporters are front-line mediators of drug resistance in cancers and represent important therapeutic targets in future chemotherapy. The crystal structure of human MRP1/ABCC1 is expected to be resolved in the near future and this will provide an insight into the SAR of MRP1/ABCC1 and allow for rational design of anticancer drugs and potent and selective MRP1/ABCC1 inhibitors.

AssetDivider : a new mediation tool in Australian family law

This article describes research in a new theory of decision support in negotiation in family law mediation. AssetDivider was based on the principles of Family_Winner. As a Negotiation Decision Support System Family_Winner takes ratings assigned to items by the parties involved and develops a list of allocations to each party; based on trade-offs inherently present in the dispute. Given advice provided from our industry partners Relationships Australia (Queensland) - RAQ, AssetDivider uses an ideal “percentage split” to guide the development of an allocation list for parties. The system has been tested informally by our contacts at RAQ, and we now look forward to extensive testing and evaluation by mediators at RAQ in the near future. We hope to report on a comprehensive evaluation which will report on the effectiveness of this program in practice.

Molecular mechanisms of inflammation : anti-inflammatory benefits of virgin olive oil and the phenolic compound oleocanthal

Chronic inflammation is a critical factor in the pathogenesis of many inflammatory disease states including cardiovascular disease, cancer, diabetes, degenerative joint diseases and neurodegenerative diseases. Chronic inflammatory states are poorly understood, however it is known that dietary habits can evoke or attenuate inflammatory responses. Popular methods to deal with inflammation and its associated symptoms involve the use of non steroidal anti-inflammatory drugs, however the use of these drugs are associated with severe side effects. Therefore, investigations concerned with natural methods of inflammatory control are warranted. A traditional Mediterranean diet has been shown to confer some protection against the pathology of chronic diseases through the attenuation of proinflammatory mediators and this has been partially attributed to the high intake of virgin olive oil accompanying this dietary regime. Virgin olive oil contains numerous phenolic compounds that exert potent anti-inflammatory actions. Of interest to this paper is the recently discovered phenolic compound oleocanthal. Oleocanthal is contained in virgin olive oil and possesses similar anti-inflammatory properties to ibuprofen. This pharmacological similarity has provoked interest in oleocanthal and the few studies conducted thus far have verified its anti-inflammatory and potential therapeutic actions. A review of the health benefits of the Mediterranean diet and antiinflammatory properties of virgin olive oil is presented with the additional emphasis on the pharmacological and anti-inflammatory properties of the phenolic compound oleocanthal.

Links between pollen, atopy and the asthma epidemic

Pollen allergy has been found in 80–90% of childhood asthmatics and 40–50% of adult-onset asthmatics. Despite the high prevalence of atopy in asthmatics, a causal relationship between the allergic response and asthma has not been clearly established. Pollen grains are too large to penetrate the small airways where asthma occurs. Yet pollen cytoplasmic fragments are respirable and are likely correlated with the asthmatic response in allergic asthmatics. In this review, we outline the mechanism of pollen fragmentation and possible pathophysiology of pollen fragment-induced asthma. Pollen grains rupture within the male flowers and emit cytoplasmic debris when winds or other disturbances disperse the pollen. Peak levels of grass and birch pollen allergens in the atmosphere correlated with the occurrence of moist weather conditions during the flowering period. Thunderstorm asthma epidemics may be triggered by grass pollen rupture in the atmosphere and the entrainment of respirable-sized particles in the outflows of air masses at ground level. Pollen contains nicotinamide adenine dinucleotide phosphate (reduced) oxidases and bioactive lipid mediators which likely contribute to the inflammatory response. Several studies have examined synergistic effects and enhanced immune response from interaction in the atmosphere, or from co-deposition in the airways, of pollen allergens, endogenous pro-inflammatory agents, and the particulate and gaseous fraction of combustion products. Pollen and fungal fragments also contain compounds that can suppress reactive oxidants and quench free radicals. It is important to know more about how these substances interact to potentially enhance, or even ameliorate, allergic asthma.

Efficacy of a referral and physical activity program for survivors of prostate cancer [ENGAGE] : rationale and design for a cluster randomised controlled trial

Background: Despite evidence that physical activity improves the health and well-being of prostate cancer survivors, many men do not engage in sufficient levels of activity. The primary aim of this study (ENGAGE) is to determine the efficacy of a referral and physical activity program among survivors of prostate cancer, in terms of increasing participation in physical activity. Secondary aims are to determine the effects of the physical activity program on psychological well-being, quality of life and objective physical functioning. The influence of individual and environmental mediators on participation in physical activity will also be determined.
Methods/Design: This study is a cluster randomised controlled trial. Clinicians of prostate cancer survivors will be randomised into either the intervention or control condition. Clinicians in the intervention condition will refer eligible patients (n = 110) to participate in an exercise program, comprising 12 weeks of supervised exercise sessions and unsupervised physical activity. Clinicians allocated to the control condition will provide usual care to eligible patients (n = 110), which does not involve the recommendation of the physical activity program. Participants will be assessed at baseline, 12 weeks, 6 months, and 12 months on physical activity, quality of life, anxiety, depression, self-efficacy, outcome expectations, goals, and socio-structural factors.
Discussion: The findings of this study have implications for clinicians and patients with different cancer types or other chronic health conditions. It will contribute to our understanding on the potential impact of clinicians promoting physical activity to patients and the long term health benefits of participating in physical activity programs.

Childhood sexual abuse and adolescent eating disorder : findings from the Victorian Adolescent Health Cohort study

Objective: To examine the relationship between childhood sexual abuse (CSA) before the age of 16 years and later onset of bulimia and anorexia nervosa symptoms in females.

Design: A longitudinal cohort study of adolescents observed from August 1992 to March 2003. The cohort was defined in a 2-stage cluster sample using 44 Australian schools in Victoria.

Setting: Population based.

Participants: A total of 1936 persons participated at least once and survived to the age of 24 years, including 999 females. The mean (SD) age of females at the start of follow- up was 14.91 (0.39) years; and at completion, 24.03 (0.55) years.

Main Exposure: Self-reported CSA before the age of 16 years was ascertained retrospectively at the age of 24 years.

Outcome Measures: Incident Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition)–defined partial syndromes of anorexia and bulimia nervosa were identified between waves 4 (mean age, 16.3 years) and 6 (mean age, 17.4 years) using the Branched Eating Disorder Test.

Results: The incidence of bulimic syndrome during adolescence was 2.5 (95% confidence interval, 0.80-8.0) times higher among those who reported 1 episode of CSA and 4.9 (95% confidence interval, 1.9-12.7) times higher among those who reported 2 or more episodes of CSA, compared with females reporting no episodes, adjusted for age and background factors. The association persisted after adjusting for possible confounders or mediators measured 6 months earlier, including psychiatric morbidity and dieting behavior. There was little evidence of an association between CSA and partial syndromes of incident anorexia nervosa.

Conclusion: Childhood sexual abuse seems to be a risk factor for the development of bulimic syndromes, not necessarily mediated by psychiatric morbidity or severe dieting.

Reaping identity meanings from an agrarian past : southern harvesters of commercially cultivated regional heritage

Extending knowledge of the cultural shaping and variegating of white identity that occurs through the commercial diffusion of identity myths, we examine the reception of Southern identity myths promoted in the oppositional narratives of New South commercial media. We characterize oppositional narratives as texts which operate by eliciting an interpretive reading that devalues rather than supports the surface narrative, and explain the duplicitous text as one intended to seduce a dominant power, while empowering and bolstering identity of a marginalized group. After elaborating how oppositional discourse can serve to reinforce the identity frame constructed by regional media producers, we report on a study examining how urban and rural Southerners read and respond to this discourse. Our findings highlight mediators in the relationship between individuals’ oppositional readings and their alignment of identity in a manner responsive to it.

Evaluating the travel, physical activity and carbon impacts of a 'natural experiment' in the provision of new walking and cycling infrastructure : methods for the core module of the iConnect study

Introduction Improving infrastructure to support walking and cycling is often regarded as fundamental to encouraging their widespread uptake. However, there is little evidence that specific provision of this kind has led to a significant increase in walking or cycling in practice, let alone wider impacts such as changes in overall physical activity or carbon emissions. Connect2 is a major new project that aims to promote walking and cycling in the UK by improving local pedestrian and cycle routes. It therefore provides a useful opportunity to contribute new evidence in this field by means of a natural experimental study.

Methods and analysis iConnect is an independent study that aims to integrate the perspectives of public health and transport research on the measurement and evaluation of the travel, physical activity and carbon impacts of the Connect2 programme. In this paper, the authors report the study design and methods for the iConnect core module. This comprised a cohort study of residents living within 5 km of three case study Connect2 projects in Cardiff, Kenilworth and Southampton, supported by a programme of qualitative interviews with key informants about the projects. Participants were asked to complete postal questionnaires, repeated before and after the opening of the new infrastructure, which collected data on demographic and socioeconomic characteristics, travel, car fuel purchasing and physical activity, and potential psychosocial and environmental correlates and mediators of those behaviours. In the absence of suitable no-intervention control groups, the study design drew on heterogeneity in exposure both within and between case study samples to provide for a counterfactual.

Ethics and dissemination The study was approved by the University of Southampton Research Ethics Committee. The findings will be disseminated through academic presentations, peer-reviewed publications and the study website (http://www.iconnect.ac.uk) and by means of a national seminar at the end of the study.

Living with prostate cancer: randomised controlled trial of a multimodal supportive care intervention for men with prostate cancer

Background: Prostate cancer is the most common male cancer in developed countries and diagnosis and treatment carries with it substantial morbidity and related unmet supportive care needs. These difficulties may be amplified by physical inactivity and obesity. We propose to apply a multimodal intervention approach that targets both unmet supportive care needs and physical activity.

Methods/design: A two arm randomised controlled trial will compare usual care to a multimodal supportive care intervention “Living with Prostate Cancer” that will combine self-management with tele-based group peer support. A series of previously validated and reliable self-report measures will be administered to men at four time points: baseline/recruitment (when men are approximately 3-6 months post-diagnosis) and at 3, 6, and 12 months after recruitment and intervention commencement. Social constraints, social support, self-efficacy, group cohesion and therapeutic alliance will be included as potential moderators/mediators of intervention effect. Primary outcomes are unmet supportive care needs and physical activity levels. Secondary outcomes are domain-specific and healthrelated quality of life (QoL); psychological distress; benefit finding; body mass index and waist circumference. Disease variables (e.g. cancer grade, stage) will be assessed through medical and cancer registry records. An economic evaluation will be conducted alongside the randomised trial.

Discussion: This study will address a critical but as yet unanswered research question: to identify a populationbased way to reduce unmet supportive care needs; promote regular physical activity; and improve disease-specific and health-related QoL for prostate cancer survivors. The study will also determine the cost-effectiveness of the intervention.

Inflammatory signaling in skeletal muscle cell growth

This thesis examines the potential beneficial role of inflammation in skeletal muscle tissue. This work establishes cyclooxygenase pathway derived prostaglandins as key anabolic signalling molecules regulating skeletal muscle cell growth and examines changes in circulating inflammatory lipid mediators and intramuscular anabolic signaling in response to acute resistance exercise in humans.

A theory of change framework for developing cross-faculty programs : an information systems perspective

Information systems (IS) is a discipline that draws upon many other disciplines to bridge theory and practice and address the information and knowledge needs of individuals, organisations and society. We propose that an ideal education in IS would be delivered via cross-faculty programs of study that are not combinations of units from different faculties and disciplines, but programs which include a coherent and cohesive set of units co-designed and co-delivered by teaching staff from more than one faculty. This allows students, and teachers, to appreciate the different content and perspectives within the same context, as they will experience in the workplace, and allow them to develop deeper understandings of the complexity that can arise in their roles as mediators and communicators in finding appropriate IT solutions. Such a model poses a radical change, and thus the framework we offer uses a ‘theory of change’ agenda.

Enhanced cytotoxic function of natural killer and natural killer T-like cells associated with decreased CD94 (Kp43) in the chronic obstructive pulmonary disease airway

Background and objective: Natural killer (NK) and natural killer T (NKT)-like cells represent a small but important proportion of effector lymphocytes that we have previously shown to be major sources of pro-inflammatory cytokines and granzymes. We hypothesized that these cells would be increased in the airway in chronic obstructive pulmonary disease (COPD), accompanied by reduced expression of the inhibitory receptor CD94 (Kp43) and increased expression of cytotoxic mediators granzyme B and perforin.
Methods: We measured NK and NKT-like cells and their expression of CD94 in the blood of COPD patients (n = 71; 30 current and 41 ex-smokers), smokers (16) and healthy controls (25), and bronchoalveolar lavage fluid (BALF) from a cohort of subjects (19 controls, 12 smokers, 33 COPD). Activation was assessed by measuring CD69 in blood and the cytotoxic potential of NK cells by measuring granzymes A and B, and using a cytotoxicity assay in blood and BALF.
Results: In blood in COPD, there were no significant changes in the proportion of NK or NKT-like cells or expression of granzyme A or NK cytotoxic potential versus controls. There was, however, increased expression of granzyme B and decreased expression of CD94 by both cell types versus controls. The proportion of NK and NKT-like cells were increased in BALF in COPD, associated with increased NK cytotoxicity, increased expression of granzyme B and decreased expression of the inhibitory receptor CD94 by both cell types.
Conclusions: Treatment strategies that target NK and NKT-like cells, their cytotoxicity and production of inflammatory mediators in the airway may improve COPD morbidity.

Associations between neighbourhood and household environmental variables and fruit consumption : exploration of mediation by individual cognitions and habit strength in the GLOBE study

Objective The present study examined associations of several home and neighbourhood environmental variables with fruit consumption and explored whether these associations were mediated by variables derived from the Theory of Planned Behaviour (TPB) and by habit strength.

Design Data of the Dutch GLOBE study on household and neighbourhood environment, fruit intake and related factors were used, obtained by self-administered questionnaires (cross-sectional), face-to-face interviews and audits.

Setting The city of Eindhoven in the Netherlands

Subjects Adults (n 333; mean age 58 years, 54 % female).

Results Multiple mediation analyses were conducted using regression analyses to assess the association between environmental variables and fruit consumption, as well as mediation of these associations by TPB variables and by habit strength. Intention, perceived behaviour control, subjective norm and habit strength were associated with fruit intake. None of the neighbourhood environmental variables was directly or indirectly associated with fruit intake. The home environmental variable ‘modelling behaviour by family members’ was indirectly, but not directly, associated with fruit intake. Habit strength and perceived behaviour control explained most of the mediated effect (71·9 %).

Conclusions Modelling behaviour by family members was indirectly associated with fruit intake through habit strength and perceived behaviour control. None of the neighbourhood variables was directly or indirectly, through any of the proposed mediators, associated with adult fruit intake. These findings suggest that future interventions promoting fruit intake should address a combination of the home environment (especially modelling behaviour by family members), TPB variables and habit strength for fruit intake.

Airway clearance of apoptotic cells in COPD

Apoptosis of bronchial epithelial cells and the phagocytic clearance of these cells by alveolar macrophages (a process termed efferocytosis) are integral processes leading to repair of airway epithelial injury. Efferocytosis allows for the removal of apoptotic material with minimal inflammation and prevents the development of secondary necrosis and ongoing inflammation. Defective efferocytosis and the increased presence of apoptotic cells have been identified in the airways of subjects with chronic obstructive pulmonary disease (COPD). There are three major potential causes for this accumulation of apoptotic cells: (i) increased apoptosis per se as a result of an increase in apoptotic mediators, (ii) defects in the recognition of apoptotic cells by AM and (iii) failure to clear the unwanted cells by the process of efferocytosis. The implications of these processes in COPD and novel treatment strategies aimed at improving clearance of apoptotic cells form the focus of the present review.